Nonrheumatic atrial fibrillation (AF) occurs in 1.5 million Americans and carries a fivefold increased risk of stroke - some 75,000 strokes yearly. In November 1989, the first phase of the SPAF Study was terminated early due to unequivocal evidence that both aspirin and warfarin were superior to placebo for stroke prevention (p<.02, 49-81% reduction). Data were insufficient to determine the relative value of aspirin vs. warfarin. Major objectives of the multicenter, randomized, ongoing SPAF Study are to: 1. Compare the efficacy/safety of warfarin vs. aspirin for stroke prevention in AF pts. a. over a 2-4 yr follow-up period to assure sustained effects. b. assessing stroke severity/functional outcome vs. treatments. 2. Identify subgroups who might differentially respond to aspirin vs. warfarin, particularly age, sex and presence of carotid artery disease. 3. Organize a collaborative meta-analysis of recent randomized antithrombotic trials. Design: SPAF is a randomized treatment-efficacy trial ongoing at 15 clinical sites testing aspirin 325mg/day vs. warfarin (prothrombin time range 1.3-1.8 control) given nonblindedly. Primary events (ischemic stroke, systemic embolism) are assessed by a blinded Events Committee. The 1050 sample size allows independent determination of efficacy in pts under age 76 (n=675) and pts over age 75 (n=375). Power to detect clinically important differences in aspirin vs. warfarin is >.8 in each age group(alpha = .05, two-sided] By June 1990, 810 pts have been entered. Entry of pts over age 75 continues until June 1991 with follow-up of all pts until December 1992. Relevance: Recent randomized trials show that warfarin anticoagulation importantly reduces the stroke risk in AF pts. SPAF proved that aspirin is also effective, but that this effect is not uniform in all subpopulations. Determination of which pts should receive aspirin vs. warfarin is a critical clinical issue, affecting millions of people with AF. SPAF is the only clinical trial likely to yield an answer in the forseeable future.